JPET

Home Help [Feedback] [For Subscribers] [Archive] [Search] [Contents]
QUICK SEARCH:   [advanced]


     

This Article
Right arrow Full Text (PDF)
Right arrow Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Adamson, G. M.
Right arrow Articles by Billings, R. E.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Adamson, G. M.
Right arrow Articles by Billings, R. E.

Tumor necrosis factor: receptor binding and expression of receptors in cultured mouse hepatocytes

GM Adamson and RE Billings

Department of Environmental Health, College of Vetinary Medicine & Biomedical Science, Colorado State University, Fort Collins.

Recombinant murine tumor necrosis factor (TNF-alpha) was labeled with 125I and used to determine the binding characteristics, internalization and intracellular degradation in cultured mouse hepatocytes. [125I]TNF- alpha bound specifically to hepatocytes and Scatchard analysis of the data indicated binding to both a low-affinity (Kd = 20 nM) high capacity (51225 sites/cell) component and high-affinity component (Kd = 4 pM), with low capacity (290 sites/cell). The extent of TNF-alpha binding to hepatocytes correlated closely with its biological activity in hepatocytes, as indexed by depletion of intracellular ATP. At concentrations lower than 0.06 nM there was minimal binding and no effect on cellular ATP, whereas maximal binding at concentrations greater than 45 nM caused 80% depletion (in comparison to controls) of hepatocyte ATP. Incubation at 37 degrees C resulted in rapid uptake, internalization and degradation of [125I]TNF-alpha. This was followed by release of degraded material from hepatocytes. Examination, by reverse transcriptase/polymerase chain reaction technology, of hepatocyte RNA extracted after the 4-hr adherence period revealed that mouse hepatocytes expressed mRNA for both TNF-alpha receptor 1 and TNF- alpha receptor 2, and that the relative abundance of TNF-alpha receptor 1 was approximately 7-fold greater than that for TNF-alpha receptor 2. Because it has been shown that these receptors have different affinities for TNF-alpha, this may explain the high- and low-affinity binding sites present on cultured mouse hepatocytes.

Volume 269, Issue 1, pp. 367-373, 04/01/1994
Copyright © 1994 by American Society for Pharmacology and Experimental Therapeutics




This article has been cited by other articles:


Home page
 Cancer Res.Home page
F. Curnis, A. Gasparri, A. Sacchi, R. Longhi, and A. Corti
Coupling Tumor Necrosis Factor-{alpha} with {alpha}V Integrin Ligands Improves Its Antineoplastic Activity
Cancer Res., January 15, 2004; 64(2): 565 - 571.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Regul. Integr. Comp. Physiol.Home page
M. Bucher, J. Hobbhahn, K. Taeger, and A. Kurtz
Cytokine-mediated downregulation of vasopressin V1A receptors during acute endotoxemia in rats
Am J Physiol Regulatory Integrative Comp Physiol, April 1, 2002; 282(4): R979 - R984.
[Abstract] [Full Text] [PDF]


Home Help [Feedback] [For Subscribers] [Archive] [Search] [Contents]
All ASPET Journals Molecular Pharmacology Pharmacological Reviews
Molecular Interventions Drug Metabolism and Disposition

Copyright © 1994 by the American Society for Pharmacology and Experimental Therapeutics.